Biology subjects

Zegarra, D.

Publications and source records attributed to Zegarra, D..

3 recordsLinked to original sources

bioRxiv2026

Potent broad-spectrum antiviral activity of the marine natural product Plitidepsin

Viruses pose a critical global health threat, yet therapeutic options remain limited. Finding drugs with broad-spectrum antiviral activity is essential to confront this threat. Here, we investigated whether plitidepsin, a marine-derived anticancer drug targeting the host eukaryotic elongation factor 1A (eEF1A), has such broad-spectrum activity. Using in vitro infection models and complementary assays (MTT, plaque-forming assays, RT-qPCR, Western blot, flow cytometry), we demonstrated that plitidepsin exhibits potent dose-dependent antiviral activity against Mayaro virus (MAYV) and Chikungunya virus (CHIKV). The compound achieved 4-6 log10 reduction in viral titers at nanomolar concentrations across multiple cell lines and viral strains. Plitidepsin protected human dermal fibroblasts from viral cytopathic effects and disrupted both entry and post-entry replication stages by suppressing viral protein expression (E1, nsP1) and RNA synthesis. The compound also demonstrated antiviral activity against other medically important arboviruses, including Una, Punta Toro, Zika, and Oropouche viruses, as well as RNA and DNA viruses such as influenza A virus, vesicular stomatitis virus, and human cytomegalovirus. These findings establish plitidepsin as a potent host-directed antiviral agent with reduced likelihood of resistance development and therapeutic potential against multiple viral families.

microbiology↗

bioRxiv2025

Broad-spectrum antiviral activity of the synthetic rocaglate zotatifin against multiple viruses

Viruses pose a significant threat to global public health, yet therapeutic options are limited. Zotatifin, a synthetic rocaglate, targets eukaryotic initiation factor 4A (eIF4A), thereby inhibiting viral protein synthesis and triggering an interferon response. Whether zotatifin exhibits broad-spectrum antiviral activity is unknown. Here we evaluated zotatifins cytotoxicity using the MTT method and its antiviral activity using plaque-forming assays, Western blot analysis, immunofluorescence, and flow cytometry across multiple cell lines and virus strains. Zotatifin demonstrated better tolerability than rocaglates rocaglamide A and CR-1-31-B. The compound exhibited potent, dose-dependent inhibition of the Mayaro virus, achieving greater than a 4-log reduction in viral titers at a 50 nM dose, regardless of the cell line or virus strain tested. In addition, zotatifin was effective to inhibit multiple arboviruses (Chikungunya, Una, and Zika), influenza A virus, vesicular stomatitis virus, and vaccinia virus. Zotatifin down-regulated viral protein synthesis for all viruses tested and analysis of gene expression using RT-qPCR revealed activation of the type I interferon pathway in zotatifin-treated cells. Taken together, these results suggest that zotatifin exhibits broad-spectrum antiviral activity against five virus families, likely via several molecular mechanisms. This work supports the potential therapeutic use of zotatifin as a pan-antiviral drug in humans.

microbiology↗

bioRxiv2023

Differential susceptibility of human microglia HMC3 cells and brain microvascular endothelial HBEC-5i cells to Mayaro and Una virus infection

Mayaro (MAYV) and Una (UNAV) are emerging alphaviruses circulating in the Americas. Earlier reports have revealed that MAYV infects different human cell lines, including synovial and dermal fibroblasts, chondrocytes, osteoblasts, astrocytes and pericytes, as well as neural progenitor cells. In this study we evaluated the susceptibility of immortalized human microglia HMC3 cells and brain microvascular endothelial HBEC-5i cells to MAYV and UNAV infection. Cytopathic effects, cell viability, viral progeny yields, and the presence of E1 and nsP1 proteins in HMC3 and HBEC-5i cells infected with several MAYV or UNAV strains were assessed using an inverted microscope, MTT assay, plaque-forming assays, and immunofluorescence or Western blot, respectively. Finally, the expression of immune response genes was analyzed using qRT-PCR. MAYV and UNAV demonstrated strong cytopathic effects and significantly reduced cell viability in HMC3 cells. Moreover, the HMC3 cells were efficiently infected regardless of the virus strains tested, and E1 and nsP1 viral proteins were detected. In contrast, only MAYV appeared to infect HBEC-5i cells, and minimal effects on cell morphology or viability were observed. Furthermore, the MAYV titer and viral protein levels were substantially lower in the infected HBEC-5i cells when compared to those of the infected microglia cells. Finally, unlike UNAV, MAYV elicited a strong expression of specific interferon-stimulated genes in microglia cells, along with pro-inflammatory cytokines implicated in the immune response. Collectively, these findings demonstrate that MAYV and UNAV are capable of infecting relevant human brain cells.

microbiology↗